The world of Phantasy Star Online 2 es takes place during the same time period as its sister title. Dr. Cohen, a famous researcher that was known for developing the breakthrough chip system, mysteriously disappeared one day during a research mission while accompanied by his body guard, Donovan, who has also gone missing. Four years later, ARKS headquarters grants Management Officer Seraphy permission to head a confidential search and rescue mission in order to retrieve the man at any cost. In her efforts of finding Dr. Cohen alive, she recruits the player character to search for any leads regarding his whereabouts while scouring several landscapes and different planets. She reveals to the player that she accepted her mission for both professional reasons and because the doctor is also her father.

Along the way, several message pods are found left behind by Dr. Cohen. Some of them offer incriminating evidence that the doctor may have allowed darkers to invade residential areas willingly, and perhaps had a hand in developing a "Type-C" chip that enhances darker strength. As they continue to search the desert, the player and Seraphy receive an emergency call from the doctor himself. Cohen warns them, calmly explaining that if ARKS continue to interfere with his research, he will retaliate with force. Due to the sudden turn of events, Seraphy is reluctantly forced to change the objective from a simple recovery mission to a custody restraint operation with permission to kill if necessary.

The team eventually discovers a hidden base on the floating continent of Amduskia. Inside, the two are granted an opportunity to speak with the alive and well Dr. Cohen. They learn that the doctor had been performing experiments on the local wildlife in his base in an attempt to remodel them. After an intense discussion, Seraphy commands several troops to thoroughly investigate the base. ARKS allows the move, but also secretly investigates the conversation that took place between her and Dr. Cohen. When they learn that her actions have been for selfish gain, they summon her to headquarters for unspecified reasons.